The long range objective of this research proposal is to more closely define in normal and obese man the roles of insulin, glucagon, and the ambient glucose concentration in the regulation of glucose and amino acid flux across the forearm and splanchnic beds. This study has become feasible because of the recent advent of somatostatin, a newly-discovered hypothalamic hormone, which, when administered systematically in man, inhibits markedly the endogenous secretion of insulin and glucagon. After somatostatin administration, plasma insulin and glucagon fall rapidly to very low levels thus allowing the investigator to then exdogenously infuse these hormones, singly and in combination, and be able to dissect apart their individual roles in regulating the metabolic processes under study. Using the hepatic vein - brachial artery -deep forearm vein catheterization technique, we can isolate the forearm skeletal muscle bed and the splanchnic (hepatic) bed and determine rates of uptake and output of glucose and amino acids and the effects of isolated changes in circulating insulin, glucagon, and glucose concentration on these parameters. Utilization of the glucose clamp technique will permit control of the blood glucose concentration thus eliminating a changing glucose concentration as a variable in these studies. Using these techniques, we wish to accomplish the following in normal man: (1) to establish the dose response relationship between insulin and the net flux of glucose and amino acids across the splanchnic and forearm beds under conditions of euglycemia and hyperglycemia; (2) to establish the effects of glucagon at sub-basal, basal, and elevated concentrations and (3) the effects of changes in arterial glucose concentration on these same parameters. Somatostatin will be infused in all studies in order that exogenous infusions of insulin, glucagon or glucose can be administered and their effects examined in the absence of changes in endogenous insulin or glucagon secretion. These studies will provide considerable insight into the hormonal regulation of glucose and amino acid flux in normal man and should more closely define the abnormalities in the hormonal control of fuel flux in obese man.